Is there a role for Crohnʼs disease-associated autophagy genes ATG16L1 and IRGM in formation of granulomas?
Copyright policy )Is there a role for Crohnʼs disease-associated autophagy genes ATG16L1 and IRGM in formation of granulomas?
Autophagy-related 16-like 1 gene (ATG16L1) and immunity-related guanosine triphosphatase gene (IRGM) are associated with Crohn's disease susceptibility and autophagy. Elimination of invading pathogens is a function of autophagy. Formation of granulomas can be attributed to impaired recognition of bacterial components by the innate immune system. This study was undertaken to elucidate whether disease-associated variants in ATG16L1 and IRGM by affecting autophagy pathways impair pathogen clearance in the cell and thereby cause increased prevalence of granulomas in Crohn's disease patients.Genotypes of the inflammatory bowel disease patient cohort consisting of 819 inflammatory bowel disease patients and over 1700 histology reports on intestinal biopsies obtained during ileocolonoscopy stating the presence or absence of granulomas were included in this case-control study.We confirm the association of the ATG16L1 variant and IRGM variants with Crohn's disease. Comparison of the genotype frequency of the ATG16L1 SNP (rs2241880) and the presence or absence of granuloma in 179 cases showed a P value of 0.16. Both variants in IRGM (rs4958847 and rs13361189) showed P values of 0.7 after comparison with granuloma prevalence in 213 cases. A total of 169 Crohn's disease patients were genotyped for both the genes, but no evidence for gene-gene interaction between ATG16L1 and IRGM and granuloma formation was found.Our Crohn's disease patient cohort showed no association of the variants in ATG16L1 or IRGM and the presence of granulomas.
- University of Amsterdam Netherlands
- University of Groningen Netherlands
- Amsterdam UMC Netherlands
- Academic Medical Center Netherlands
EXPRESSION, autophagy, SUSCEPTIBILITY LOCI, PATHOGENESIS, Autophagy-Related Proteins, INNATE, Polymorphism, Single Nucleotide, Cohort Studies, Crohn Disease, inflammatory bowel disease, GTP-Binding Proteins, Autophagy, ADAPTIVE IMMUNITY, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, granuloma, Granuloma, Colonoscopy, Inflammatory Bowel Diseases, Case-Control Studies, Carrier Proteins, genetic susceptibility
EXPRESSION, autophagy, SUSCEPTIBILITY LOCI, PATHOGENESIS, Autophagy-Related Proteins, INNATE, Polymorphism, Single Nucleotide, Cohort Studies, Crohn Disease, inflammatory bowel disease, GTP-Binding Proteins, Autophagy, ADAPTIVE IMMUNITY, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, granuloma, Granuloma, Colonoscopy, Inflammatory Bowel Diseases, Case-Control Studies, Carrier Proteins, genetic susceptibility
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